The use of previous anorectic medications and the combined use of the anorectic medications fenfluramine and phentermine (Fen-Phen) have been associated with varying degrees of valvular regurgitation and pulmonary hypertension. More recent reports have suggested a lower incidence of both than was previously reported. Comparisons of patients with similar body mass index (BMI) have been missing as well as information regarding chamber dimensions and pressures. Using transthoracic 2D, M-mode, and Doppler echocardiography, 57 men and women (30 Fen-Phen and 27 BMI-matched individuals/BMIMCG) were studied to determine their chamber dimensions, wall motion, diastolic function, valvular abnormalities, left ventricular ejection fractions (LVEFs), and pulmonary artery pressures (pAPs). The 30 Fen-Phen subjects were studied shortly after discontinuing the medications and again 6 to 12 months later. The results in these subjects were then compared with the valvular findings of 660 randomly selected cardiac patients with non-Fen-Phen-induced heart disease (NFPHD). Valvular regurgitation was greatest among patients who had recently discontinued the use of Fen-Phen (EFP) with 57% of all valves having regurgitation, 87.5% of which were "mild." These same individuals also had the largest left ventricles at end (LVEDD) diastole (5.03 +/-0.22 cm) and systole (LVESD). The LVESDs were statistically larger (p <or= 0.05) than that seen in the other groups, while at the same time their LVEFs were statistically (p <or= 0.01) lower (53.44 +/-9.48%). These same patients had statistically (p <or= 0.05) greater PAPs (29.21 +/-10.52 mm Hg), which were associated with a lower incidence rate (14%) of pulmonic regurgitation (PR). The number of people with aortic regurgitation (AR), statistically (p <or= 0.05) decreased (40%) as the duration of time since discontinuing Fen-Phen increased (late Fen-Phen/LFP). However, for those individuals who continued to have AR, there was an increase in the number of people who progressed from mild to moderate AR, with an associated increase in LVEDD (5.41 +/-0.55 cm), LVESD (3.51 +/- 0.84 cm), and LVEF (63.45 +/-15.25%). The LFP studies showed a statistical (p <or= 0.001) increase in PR with a subsequent drop in PAPs from 29.21 +/-10.52 mm Hg in the early (EFP) studies to 14.02 +/-1.35 mm Hg, which was augmented with weight-bearing and Valsalva maneuvers. The reduction in the percentage of individuals with valvular regurgitation and pulmonary hypertension appears to be due to changes in the heart valves, pressures, and chamber size. The incidence of tricuspid and mitral regurgitation decreased with time, while pulmonic and aortic regurgitation tended to increase or become more severe when present. Dilatation of the pulmonary ring, resulting from elevated pulmonic pressures with subsequent pulmonary regurgitation and reduction in pulmonary artery pressures, appears to be a functional change in the hearts of these individuals with unknown long-term consequences.